1. Technical Field
The present invention is generally related to the field of biologically derived polymers for use in drug delivery and tissue engineering, and is more specifically related to biologically derived polymers that facilitate the solubilization and protection of small molecules for use in drug delivery, ranging from the delivery of common essential vitamins to complex small molecule therapeutics.
2. Prior Art
Advancements in drug delivery have often been challenged with the problem of controlled targeting. To date, passive and active targeting strategies have been operating with a shroud, hiding the journey that an active compound takes upon introduction into the living system. Common passive strategies take advantage of the enhanced permeability and retention (EPR) effect observed in sites of tumor growth. Maeda, H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41, 189-207 (2001). Other strategies rely on surgically focused triggering mechanisms such as hyperthermally controlled assembly of carrier agents, coupled to release of active compounds. Yatvin, M. B., Weinstein, J. N., Dennis, W. H. & Blumenthal, R. Design of liposomes for enhanced local release of drugs by hyperthermia. Science 202, 1290-1293 (1978). All of these strategies rely on control of delivery at the end-point site; no component of the current solutions addresses the possible path that the delivery agent and/or active compound may take en route. Thus, questions of in vivo degradation, absorption, accumulation, and metabolization of the drug still remain questions for every drug and delivery agent thereof. In addition, drug delivery, ranging from the delivery of common essential vitamins to complex small molecule therapeutics, is often stymied by issues of compound solubility and point-of-use activity.
In the field's attempt to monitor the drug delivery process, research groups have attempted to radioactively label drug delivery vehicles based on ELP sequences and monitor the in vivo environment via sampling and subsequent ex vivo measurement. Liu, W., Dreher, M. R., Chow, D. C., Zalutsky, M. R. & Chilkoti, A. Tracking the in vivo fate of recombinant polypeptides by isotopic labeling. J Control Release 114, 184-192, (2006). Similarly, epitopic labeling of drug delivery vehicles has been attempted, but observation is still an ex vivo process. Ong, S. R. et al. Epitope tagging for tracking elastin-like polypeptides. Biomaterials 27, 1930-1935, (2006). Recently, paramagnetic chemical exchange saturation transfer (PARACEST) technology has been developed to enable competitive binding experiments to be monitored non-quantitatively in vivo, Ali, M. M., Yoo, B. & Pagel, M. D. Tracking the relative in vivo pharmacokinetics of nanoparticles with PARACEST MRI. Mol Pharm 6, 1409-1416, (2009); however, this MRI technique requires the use of complexing active compounds to contrast agents containing rare heavy metals, driving the price and immunological complexity of the procedure up significantly.
Accordingly, there is a need for biologically derived polymers that facilitate the solubilization and protection of small molecules for use in drug delivery, ranging from the delivery of common essential vitamins to complex small molecule therapeutics. It is to this need and others that the present invention is directed.